The overall objective of this research program is to probe further into the biochemical perturbations of diseases involving the last stages of human blood coagulation, namely the formation and crosslinking of fibrin. It is the long-term goal of this research to define the roles of fibrinogen and factor XIII both in health and in disease states. The specific goal of this project is to study certain interrelated structural and functional aspects of cross linking, namely the characterization of crosslinking sites in the alpha-chain of fibrin, the interaction of fibrinogen and factor XIII with calcium, the role of platelet factor XIII in the formation of the circulating plasma zymogen complex, and the modulation of these procoagulants and their cleavage products during fibrin formation and crosslinking. Characterization of spontaneously occurring human antibodies directed against factor XIII as well as the definition of the biochemical lesion in a dysfibrinogen (fibrinogen Chapel Hill) will also receive focal attention in this research.